Chemoradiotherapy has been in use for pancreatic cancer in the adjuvant and definitive settings, but the prognosis remains poor. Recently, neoadjuvant chemoradiation has been proposed for patients with resectable or borderline resectable pancreatic cancer to improve chances for a complete resection. Unfortunately, the ability to non-invasively assess treatment response in pancreatic cancer to neoadjuvant therapy is limited. While computed tomography (CT) is routinely used to assess pancreatic tumor response following chemoradiation, studies suggest that CT-detected responses are infrequent and underestimate the true rate of biologic response. Recent research at our institution has focused on assessing treatment response in brain, breast, and metastatic prostate cancer with diffusion MRI, an imaging tool which utilizes magnetic resonance pulse sequences to measure the apparent diffusion coefficient (ADC) of water, which represents the mobility of water within tissues at the cellular level. Loss of cell membrane integrity due to tumor cell death reduces the diffusion restrictions of water and increases the ADC. Therefore, diffusion MRI has the potential to measure early cellular changes that occur in response to successful therapies. Our imaging group has recently demonstrated that diffusion MRI is an early predictor not only of therapeutic response, but also of overall survival in patients with high grade brain tumors. Therefore, we hypothesize that diffusion MRI can be successfully used to assess treatment response in carcinoma of the pancreas. The long-term goal of this proposal is to test the utility of diffusion MRI in patients undergoing neoadjuvant chemoradiotherapy in a formal phase II trial. Herein, we propose to generate the data needed for the design of such trial. The specific aim of this pilot study is to characterize pancreatic tumor diffusion coefficients before and after neoadjuvant chemoradiation, and to correlate therapy-induced changes in pancreatic tumor ADCs with histopathologic analysis of resected tumors. As a secondary objective, we will correlate changes in diffusion imaging with CT- determined responses (per RECIST criteria) as well as alterations in tumor marker levels. If diffusion MRI is demonstrated to be a reliable assessment of pancreatic tumor response, it could become a valuable tool not only for determining which patients can undergo successful tumor resection, but also for the evaluation of efficacy of new treatment regimens in future clinical trials. PROJECT HEALTH RELEVANCE: Current imaging methods often underestimate the frequency and degree of treatment response in pancreatic cancer. Diffusion MRI is a novel imaging tool which has the potential to measure cellular changes that occur in response to successful therapies, such as chemoradiation. The goal of this study is to assess the utility of diffusion MRI in assessing treatment responses in patients with pancreatic cancer. Once we have shown that diffusion MRI is a good tool for assessing response in pancreatic cancer, this test will have wide applicability in patients with borderline-resectable, unresectable, and metastatic pancreatic cancer, and will assist in evaluating any future experimental treatment.